Beta-amyloid protein increases the vulnerability of cultured cortical neurons to excitotoxic damage.
Glutamate neurotoxicity may be an underlying pathological mechanism contributing to neuronal cell loss in a variety of conditions including Alzheimer's disease (AD). In this study, we examined whether the beta-amyloid protein found in the neuritic plaques of AD alters the susceptibility of neurons to excitotoxic damage. While mature cortical neurons exposed to beta-amyloid protein for 2-4 days did not appear to be damaged, their vulnerability to low-intensity exposure to glutamate, N-methyl-D-aspartate, and kainate increased, suggesting that this mechanism may contribute to the neurodegeneration seen in AD.
Koh
J Y
JY
Department of Psychobiology, University of California, Irvine 92717.
Yang
L L
LL
Cotman
C W
CW
D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D005971:Glutamates / Q000633:toxicity; D007608:Kainic Acid / Q000633:toxicity; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D016202:N-Methylaspartate / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D005971:Glutamates; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D007608:Kainic Acid